Flow Sensitive Ion Channels in Vascular Endothelial Cells: Mechanisms of Activation and Roles in Mechanotransduction.

The purpose of this review is to evaluate the current knowledge about the mechanisms by which mechanosensitive ion channels are activated by fluid shear stress in endothelial cells. We focus on three classes of endothelial ion channels that are most well studied for their sensitivity to flow and roles in mechanotransduction: inwardly-rectifying K⁺ channels, Piezo channels and TRPV channels. We also discuss the mechanisms by which these channels initiate and contribute to mechanosensitive signaling pathways. Three types of mechanisms have been described for flow-induced activation of ion channels: 1) through interaction with apical membrane flow sensors, such as glycocalyx, which is likely to be deformed by flow, 2) directly by sensing membrane stretch that is induced by shear stress, or 3) via flow-sensitive channel-channel or lipid channel interactions. We also demonstrate the physiological role of these channels and how they are related to cardiovascular and neurological diseases. Further studies are needed to determine how these channels function cooperatively to mediate the endothelial response to flow.